Three-drug regimen during pregnancy more protective against vertical HIV transmission

Women who received a three-drug regimen during pregnancy were less likely to transmit HIV to their child compared with women who received one drug during pregnancy and two more after birth, according to an NIH press release.

To determine the safest approach to reducing risk for HIV transmission from mother to child during pregnancy and after delivery, Mary Glenn Fowler, MPH, of Johns Hopkins University in Baltimore, and colleagues began the Promoting Maternal-Infant Survival Everywhere (PROMISE) study in 2010.

The study cohort included 3,500 pregnant or postpartum women with HIV who did not qualify to receive anti-HIV treatment because their CD4 T-cell count exceeded the level at which ART is recommended and 3,200 children of these mothers. Study participants were from India, Malawi, South Africa, Tanzania, Uganda, Zambia and Zimbabwe.

Mothers received either zidovudine at least 14 weeks into pregnancy, a single dose of nevirapine during labor and tenofovir and emtricitabine for two weeks after delivery, or a three-drug regimen at least 14 weeks into pregnancy. Study participants could receive one of two three-drug regimens.

One regimen, referred to as the lamivudine combination, consisted of lamivudine, zidovudine and ritonavir-boosted lopinavir. The other three-drug regimen consisted of tenofovir, emtricitabine and ritonavir-boosted lopinavir and was considered the tenofovir combination.

Overall, women who received a three-drug regimen exhibited a significantly lower rate of mother-to-child HIV transmission during pregnancy or delivery. Approximately 0.5% of infants whose mothers received the lamivudine combination developed HIV while 0.6% of infants whose mothers received the tenofovir combination developed HIV. In contrast, approximately 1.8% of infants whose mothers were treated before, during and after delivery developed HIV.

The lamivudine combination was safer than other regimens, according to an independent data and safety monitoring board, who reviewed the current PROMISE study findings. Women who received the lamivudine combination had fewer severe adverse outcomes — including very low birth weight, very premature delivery, stillbirth, spontaneous abortion and major birth defects — compared with mothers who received the tenofovir combination or treatment before, during and after delivery.

However, some adverse outcomes, such as birth weights less than 2, 500 grams and preterm delivery at less than 32 weeks gestation, were more common among mothers who received three-drug regimens vs. those who received treatment before, during and after delivery.

Anthony S. Fauci

The PROMISE study is ongoing. Study participants will be followed until 2 years after the last child is born to further evaluate safety and efficacy of anti-HIV drug regimens taken during the breastfeeding period. Researchers will also assess maternal health after the breastfeeding period. All infants are given a daily dose of nevirapine until age 6 weeks and those who develop HIV from their mother are given combination anti-HIV treatment.

“We now have the gold standard of evidence — data from a randomized clinical trial — supporting a three-drug regimen as the preferred approach for preventing HIV transmission from an infected mother to her baby during pregnancy and delivery,” Anthony S. Fauci, MD, director of the NIAID, said in a press release. “This is another important step in our efforts to define the best approaches toward the goal of eliminating mother-to-child HIV transmission globally.”

Disclosure: The PROMISE study is conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trials, funded by the NIAD, NICHD and the National Institute of Mental Health at the NIH.